骨肉瘤（OS）是常见的原发性骨癌病，主要影响儿童和年轻成年人。为了增强标准化疗法，我们研究了使用间充质干细胞（MSCs）衍生的蛋白组和OS升高蛋白质进行蛋白质为基础的治疗的可能性。虽然从MSCs收集的条件培养基（CM）没有呈现出抗肿瘤能力，但是通过激活PKA将MSCs转化为诱导性抑瘤细胞（iTSCs）。在小鼠模型中，直接和羟基烷基辅助下的CM抑制了肿瘤诱导的骨质破坏，其效果与顺铂相加。CM富含卡钙素等蛋白质，它通过与CD47相互作用发挥作为胞外抑瘤剂的作用。值得注意的是，CALR转录本的水平在OS组织中升高，与其他抑瘤蛋白质（包括组蛋白H4和PCOLCE）一起发挥作用。PCOLCE通过与淀粉样前体蛋白相互作用发挥胞外抑瘤蛋白质的作用，淀粉样前体蛋白是一种具有低生存率的预后OS标记。结果支持了利用OS转录组进行OS治疗的悖论策略的可能性。 © 2023，Li等。

Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS.© 2023, Li et al.